title: Structure-function relationships in methionine adenosyltransferases.
abstract: Methionine adenosyltransferases (MATs) are the family of enzymes that synthesize the main biological methyl donor, S-adenosylmethionine. The high sequence conservation among catalytic subunits from bacteria and eukarya preserves key residues that control activity and oligomerization, which is reflected in the protein structure. However, structural differences among complexes with substrates and products have led to proposals of several reaction mechanisms. In parallel, folding studies begin to explain how the three intertwined domains of the catalytic subunit are produced, and to highlight the importance of certain intermediates in attaining the active final conformation. This review analyzes the available structural data and proposes a consensus interpretation that facilitates an understanding of the pathological problems derived from impairment of MAT function. In addition, new research opportunities directed toward clarification of aspects that remain obscure are also identified.
authors.affiliation: Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: Markham
authors.forename: M A
authors.initials: MA
authors.lastname: Pajares
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D008715:Methionine / Q000378:metabolism; D008716:Methionine Adenosyltransferase / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D007527:Isoenzymes; D021122:Protein Subunits; D012436:S-Adenosylmethionine; D008715:Methionine; D008716:Methionine Adenosyltransferase